Lyme disease is a systemic tick-borne illness, first reported in the U.S. in the early 1970's, and characterized by a distinctive skin lesion, erythema chronicum migrans (ECM), which is frequently accompanied by headache, stiffness, fever, joint pain, malaise and fatigue. If untreated the disease can also be characterized by the subsequent development of neurological, cardiac and arthritic complications.
The etiological agent believed to be responsible for Lyme disease is a spirochete bacteria first isolated in 1982 from Ixodes dammini ticks. The spirochete has since been named Borrelia burgdorferi. Various subspecies and strains of this organism have been identified, but their interrelationship has still not been finally determined.
While the primary vector for the disease seems to be the aforementioned tick, Bosler reports the detection, by dark-field microscopy, and culturing of B. burgdorferi in the urine of the rodent Peromyscus leucopus, and suggests that urine may be a vehicle for non-tick transmission of the disease (p. 12, Second International Symposium on Lyme Disease and Related Disorders, Compendium of Abstracts, Hygiene Institute of the University of Vienna, 1985, hereinafter "1985 Symposium"). Similarly Burgess (1985 Symposium, p. 13) suggests that contact exposure between dogs can result in infection in an experimental setting.
Efforts are ongoing in the scientific community to characterize various isolates from the disease in order to identify different strains of B. burgdorferi, and to ascertain the relationship of their differences with the different clinical manifestations of the disease that are found around the world.
Such efforts frequently involve characterization, e.g., by the use of monoclonal antibodies, of the various major protein constituents of B. burgdorferi, see e.g., Barbour et al, J. Inf. Dis. 152:478-484 (1985), Barbour (185 Symposium, p. 24) and Wilske (1985 Symposium, p. 25).
Lyme disease is typically diagnosed based on the results of serological and/or clinical findings. Serological findings generally involve assays for the presence of antibodies to B. burgdorferi in the sera of patients suspected of having the disease. See, e.g., (Wilkinson, pp. 117-122, Lyme Disease, First International Symposium, The Yale J. Biol. Med., 1984 (hereinafter "1984 Symposium")).
Clinical assessment of Lyme disease is currently the more common means of diagnosing the disease and is most often accomplished by finding a history of ECM and other symptoms associated with the disease. Misdiagnoses of the disease are a problem in view of the close similarity of Lyme disease with other diseases, and because of other factors, e.g., late, sub-clinical, or variable expression of symptoms.
There exists a need for a reliable, rapid, inexpensive and non-invasive method for the diagnosis of Lyme disease. There are many situations in the diagnosis and treatment of Lyme disease where even a reliable test having a low level of false positives would be extremely valuable by itself, and particularly if used in conjunction with other tests that could be used to eliminate the false positives, or with clinical findings to identify the true positives.
Researchers have attempted to correlate the presence of the disease with the identification of B. burgdorferi in various body tissues or fluids, e.g., by histological and/or cultural evaluation of samples. Such evaluations can be performed, for instance, by microscopy or by the recovery, i.e., isolation and cultivation, of the organism from tissues or fluids.
B. burgdorferi has been isolated and cultivated from the blood, skin, and cerebrospinal fluid of patients with Lyme disease. See, e.g., Steere et al, New England J. Med. 308:733-740 (1983) and Steere et al, 1984 Symposium, pp 107-110. The isolation and cultivation of B. burgdorferi is itself frequently a difficult, time-consuming and problematic undertaking however, see, e.g., A. G. Barbour, 1984 Symposium, pp. 71-75. The identity of the recovered organisms as being B. burgdorferi was verified in Steere et al (1983) by their reactivity with a monoclonal antibody that had been made against the original isolate of the organism responsible for Lyme disease.
In both references of Steere et al the researchers were unable to isolate any B. burgdorferi spirochetes from either lymph-node aspirates or the urine of patients having Lyme disease.